The field of this invention is contrast agents for magnetic resonance imaging (MRI). More specifically, this invention relates to intravascular contrast agents.
Magnetic resonance imaging has proven to be a very important imaging modality for diagnostic radiology. The high intrinsic contrast of living tissue available with MRI has allowed the radiologist to identify pathology which was previously unseen. However, MRI has its limitations. For example, MRI has been unable to evaluate organ function or perfusion, locate acute internal hemorrhage not associated with organ displacement, or distinguish a lesion (such as tumor) from surrounding edema.
Contrast agents are valuable in traditional radiologic methodologies. Following the advent of MRI, researchers began to investigate the use of contrast agents with this imaging modality. Animal research and preliminary human studies have demonstrated that contrast agents can increase the diagnostic capabilities of MRI.
Metal chelates, such as Gd-DTPA, and nitroxide stable free radicals (NSFRs) are two classes of MRI contrast agents currently receiving attention. These contrast agents have been found useful for certain MRI examinations. However, Gd-DPTA has a molecular weight of 590, and therefore is rapidly distributed throughout the extracellular fluid space. Brasch et al., AJR (1984) 143:215-224. Further, although Gd-DTPA acts as a marker of perfusion at 90 seconds postinfusion, it is not possible to utilize this property in vivo because of the lengthy scanning times MRI requires. See Wesbey et al., Radiology (1984) 153:165-169.
"TES," a piperidinyl NSFR derivative, is an example of the second class of MRI contrast agents currently being studied. However, like Gd-DTPA, TES is a small molecular weight compound and rapidly leaves the vascular compartment following intravenous injection. Brasch et al., Radiology (1983) 147: 773-779.
A proton magnetic resonance imaging contrast agent which remains for an appreciable time in the intravascular space is not presently available. Development of contrast agents specifically for the blood pool should markedly increase the clinical utility of MRI.